Sertraline hydrochloride, (1S-cis)-4-(3,4 dichlorophenyl)-1,2,3,4-tetrahydro-N-methyl-1-naphthalenamine hydrochloride, having the formula is approved, under the trademark Zoloft®, by the U.S. Food and Drug Administration, for the treatment of depression, obsessive-compulsive disorder and panic disorder.
U.S. Pat. No. 4,536,518 (“the '518 patent”) describes the preparation of sertraline hydrochloride with a melting point of 243-245° C. by treating an ethyl acetate/ether solution of the free base with gaseous hydrogen chloride. The solid state properties of the sertraline hydrochloride so produced are not otherwise disclosed.
According to U.S. Pat. No. 5,248,699 (“the '699 patent”), the sertraline hydrochloride produced by the method of the '518 patent has a crystalline form denominated “Form II.” The '699 patent discloses four other polymorphs designated Forms I, III, IV, and V.
The present invention includes new polymorphic forms of sertraline hydrochloride. Polymorphic forms of a compound can be distinguished in a laboratory by X-ray diffraction spectroscopy and by other methods such as, infrared spectrometry. It is desirable to investigate all solid state forms of a drug, including all polymorphic forms, and to determine the stability, dissolution and flow properties of each polymorphic form. For a general review of polymorphs and the pharmaceutical applications of polymorphs see G. M. Wall, Pharm Manuf. 3, 33 (1986); J. K. Haleblian and W. McCrone, J. Pharm. Sci., 58, 911 (1969); and J. K. Haleblian, J. Pharm. Sci., 64, 1269 (1975), all of which are incorporated herein by reference.
Commonly-assigned, co-pending U.S. patent application Ser. No. 09/448,985 filed Nov. 24, 1999, which is incorporated herein by reference, discloses novel methods of making sertraline hydrochloride Form V that were discovered after unsuccessful attempts at sublimation. One of the methods disclosed in that application involves crystallization from an acidic hexane and/or isopropanol solvent system that can be made acidic by addition of concentrated hydrochloric acid in lieu of gaseous hydrochloric acid. The co-pending application also discloses other new sertraline hydrochloride forms that have been designated Forms VI, VII, VIII, IX and X.